The main symptom of atopic dermatitis (AD) is unbearable itching. Patients with mild AD who have other diseases are usually not candidates for treatment by biologists. However, modern topical medications often fail to control itching. To help these patients, American dermatologists have investigated a new approach: correcting disturbed skin flora. It is well known that AD patients have an overrepresented S. aureus in their skin microbiome.
ammonia oxidizing bacteria
In search of an effective solution, the researchers isolated a strain of Nitrosomonas (abbreviated B244) that was successful against Staphylococcus. These bacteria oxidize ammonia (NH3) to nitrogen oxides (NO) and nitrite (NO2-)—two compounds known for their antimicrobial activity. B244 can reduce the survival of pathogenic bacteria including Staphylococcus aureus and thus have a positive effect on the composition of the skin microbiota. Furthermore, B244 reduced proinflammatory Th2-associated cytokines IL-4, IL-5, and IL-13 associated with AD pathology in vitro.
antibacterial and anti-inflammatory
Nitrosomonas is not virulent. Together with its metabolic and antibacterial activity, this makes this bacterial strain an attractive candidate for topical application of nitric oxide and nitrite.
mild AD, severe pruritus
To see whether it might also help fight AD itch, US researchers tested 547 adults with mild to moderate AD with moderate to severe itch in a randomized, placebo-controlled, double-blind phase IIb study.
Patients received a low dose (1 x 1010/ml) or high (4 x 1010/ml) of bacteria or vehicle as a spray, spray twice a day on the affected skin area. The primary endpoint of the survey after four weeks was change in itching, as measured on the Worst Itching Numerical Rating Scale (WI-NRS) on a scale from 0 (no itching) to 10 (worst itching).
Advantages of spraying B244 after two days
Results: After 4 weeks, both doses of B244 had about the same effect. The mean WI-NRS score at study entry was over 8. After four weeks of treatment with the Verum spray, the value fell by 2.8 points, compared with a 2.1 point drop for the placebo. The difference between the groups was 34%, which was statistically significant.
With the B244-enriched spray (both high-dose and low-dose groups), 31% of patients improved by at least 4 points from baseline, compared with 22% of the placebo group, and their pruritus symptoms decreased at WI-NRS 4 points.
It is noteworthy that the effect of B244 was exerted rapidly: after two days, a clear advantage was observed in the verum group.
Skin appearance is also improved
The researchers also assessed overall changes in atopic dermatitis symptoms: Skin appearance after B244 spray was significantly improved on both the Investigator’s Global Assessment (IGA) and the Eczema Area and Severity Index (EASI).
B244 was well tolerated with no serious side effects. Adverse reactions were generally infrequent, mild, and generally transient; the most common complaint was headache. This occurred in 3% of patients on high doses of B244.
Based on their results, the authors recommend the development of N. eutropha-enriched sprays as a well-tolerated and fast-acting topical treatment option for the treatment of pruritus in atopic dermatitis.
The study was funded by AOBiome Therapeutics.
author: Angelica Ram-Fisher
fountain: Galbe list
refer to:
1. Silverberge et al. (2023): Efficacy and safety of topical application of therapeutic ammonia-oxidizing bacteria in adults with mild-to-moderate atopic dermatitis and moderate-to-severe pruritus: a randomized, double-blind, placebo-controlled, dose-ranging study , Phase 2b trial. eClinicalMedicine 2023 (online). DOI: 10.1016/j.eclinm.2023.102002.